POS0697 OPHTHALMOLOGICAL ADVERSE EVENTS UNDER JAK: CASE ANALYSIS OF THE EUROPEAN PHARMACOVIGILANCE DATABASE
Authors: S. Hecquet, M. B. Rabier, M. Lepelley, M. Chouk, F. Verhoeven, C. Prati, D. Wendling
Journal: Annals of the Rheumatic Diseases (2022)

Background Ophthalmological manifestations in rheumatic diseases include dry syndrome, scleritis, episcleritis, uveitis and peripheral ulcerative keratitis (PUK). Among the target therapies, JAK inhibitors (JAKinhib) are the most recent to have been approved in rheumatic diseases, rheumatoid arthritis (RA) and spondyloarthritis (SpA), but also in other indications such as inflammatory bowel disease. Objectives The aim of this work is to describe and characterise ophthalmological events in patients exposed to JAKinhib based on European pharmacovigilance (PV) data. Methods The ophthalmological manifestations that appeared under JAK inhib were extracted from the European PV database (April 2020), EUDRAVIGILANCE following a request addressed to the National Drug Safety Agency carried out according to the following MedDRA classification “SOC eye disorders and BARICITINIB” and “SOC eye disorders and TOFACITINIB”. Results A total of 1411 patients with ophthalmological adverse events (AEs) were identified with JAKinhib. 103 with BARICITINIB (81 women, mean age 59.7 years), 1308 with TOFACITINIB (1116 women, mean age 64.7 years). Among these AEs, 58% were reported by medical and paramedical staff and 42% were reported by patients. JAKinhib was initiated mainly in patients with RA (1070 patients), SpA (26 patients) and ulcerative colitis (UC) (27 patients). Of the reported AEs, 10% were inflammatory disorders of the anterior or posterior segments of the eye [51 uveitis (40 RA, 1 SpA, 1 RCUH, 1AJI, 8 undetermined (n.d.)), 49 corneal ulcerations (38 RA, 2 RCHU, 9 n.d.), 28 scleritis (20 RA, 8 n.d.), 13 keratitis (8 RA, 1 SpA, 1 Crohn’s, 3 n.d.)]. Visual loss and complete loss of vision were also reported in 200 patients. Finally, retinal detachment, retinal vascular thrombosis, cataracts and unspecified ophthalmological AEs were observed in 27, 25, 329 and 185 patients respectively. The mean time to onset of inflammatory ophthalmological events was 258 days after initiation of treatment (Table 1). Table 1. Ophthalmological adverse events with JAK inhibitors BARICITINIB TOFACITINIB Mean delay (in days) n=103 n=1308 Inflammatory involvement 2 (2) 26 (2) 190±197 Scléritis, n (% ) 8 (8) 41 (3) 321±405 Corneal ulcération, n (% ) 1 (1) 50 (4) 292±296 Uvéitis, n (% ) 2 (2) 11 (1) 172±244 Kératitis Decreased visual acuity, n (% ) 10 (10) 118 (9) 165±193 Visual loss, n (% ) 0 72 (5) 74±83 Red eyes, n (% ) 14 (14) 51 (4) 80±149 Dry eyes, n (% ) 15 (15) 136 (10) 166±454 Photophobia, n (% ) 3 (3) 14 (1) 272±519 Retinal detachment, n (% ) 1 (1) 26 (2) 461±360 Retinal vascular thrombosis, n (% ) 3 (3) 22 (2) 367±490 Retinal haemorrhage, n (% ) 2 (2) 19 (1) 168±199 Cataract, n (% ) 9 (9) 320 (24) Glaucoma, n (% ) 0 77 (6) 432±360 Age related macular degeneration (% ) 0 34 (3) 351±549 Unspecified ophthalmological AEs 8 (8) 177 (14) 126±184 Conclusion Ophthalmological manifestations under JAK inhib seem rare but not exceptional. The rheumatologist must be made aware of them in order to discuss the potential imputability of the treatment and to report these manifestations to the pharmacovigilance structures. A detailed history, exclusion of infections and histopathological evaluation of the lesions are recommended to ensure that a differential diagnosis is not ignored. Topical treatments, and if necessary, discontinuation of the drug and switching to another targeted therapy may be considered. Discontinuation of JAKinhib appears to be warranted pending ophthalmologic advice. Disclosure of Interests None declared